title: β,β-carotene 15,15'-monooxygenase and its substrate β-carotene modulate migration and invasion in colorectal carcinoma cells.
abstract: BACKGROUND
  β,β-Carotene 15,15'-monooxygenase (BCMO1) converts β-carotene to retinaldehyde. Increased β-carotene consumption is linked to antitumor effects. Retinoic acid reduces the invasiveness in cancer, through inhibition of matrix metalloproteinases (MMPs). In our studies of a mouse model that develops intestinal tumors after low dietary folate, we found reduced BCMO1 expression in normal preneoplastic intestine of folate-deficient tumor-prone mice.
  
  
  OBJECTIVE
  Our goal was to determine whether BCMO1 expression could influence transformation potential in human colorectal carcinoma cells, by examining the effect of BCMO1 modulation on cellular migration and invasion, and on expression of MMPs.
  
  
  METHODS
  LoVo colon carcinoma cells were transfected with BCMO1 small interfering RNA (siRNA) or scrambled siRNA. Migration and invasion were measured, and the expression of BCMO1, MMP7, and MMP28 was assessed by quantitative reverse-transcriptase polymerase chain reaction. These variables were also measured after treatment of cells with retinoic acid, 5-aza-2'-deoxycytidine, folate-depleted/high-methionine medium, and β-carotene.
  
  
  RESULTS
  Retinoic acid decreased the migration, invasion, and expression of MMP28 mRNA. Transfection of cells with BCMO1 siRNA inhibited BCMO1 expression, enhanced migration and invasion, and increased expression of MMP7 and MMP28. 5-Aza-2'-deoxycytidine decreased, whereas folate-depleted/high-methionine medium increased invasiveness. β-Carotene increased BCMO1 expression and reduced invasiveness with a decrease in expression of MMP7 and MMP28.
  
  
  CONCLUSIONS
  Inhibition of BCMO1 expression is associated with increased invasiveness of colon cancer cells and increased expression of MMP7 and MMP28. β-Carotene can upregulate BCMO1 and reverse these effects. These novel associations suggest a critical role for BCMO1 in cancer and provide a mechanism for the proposed antitumor effects of β-carotene.
authors.affiliation: Departments of Human Genetics and Pediatrics, McGill University, and the Montreal Children's Hospital site of the McGill University Health Centre Research Institute, Montreal, Canada.
authors.forename: Diep Ngoc Thi
authors.initials: DN
authors.lastname: Pham
authors.forename: Daniel
authors.initials: D
authors.lastname: Leclerc
authors.forename: Nancy
authors.initials: N
authors.lastname: Lévesque
authors.forename: Liyuan
authors.initials: L
authors.lastname: Deng
authors.forename: Rima
authors.initials: R
authors.lastname: Rozen
mesh_terms: D045744:Cell Line, Tumor; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation; D019207:beta Carotene / Q000494:pharmacology*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019207:beta Carotene; D014212:Tretinoin; D005492:Folic Acid; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase; C424663:MMP28 protein, human; D053505:Matrix Metalloproteinases, Secreted; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7